Shearing friction behaviour of synthetic polymers compared to a functionalized polysaccharide on biomimetic surfaces: models for the prediction of performance of eco-designed formulations.

The substitution of natural, bio-based and/or biodegradable polymers for those of petrochemical origin in consumer formulations has become an active area of research and development as the sourcing and destiny of material components becomes a more critical factor in product design. These polymers often differ from their petroleum-based counterparts in topology, raw material composition and solution behaviour. Effective and efficient reformulation that maintains comparable cosmetic performance to existing products requires a deep understanding of the differences in frictional behaviour between polymers as a function of their molecular structure. In this work, we simulate the tribological behaviour of three topologically distinct polymers in solution with surfactants and in contact with hair-biomimetic patterned surfaces. We compare a generic functionalized polysaccharide to two performant polymers used in shampoo formulations: a strongly positively charged polyelectrolyte and a zwitterionic copolymer. Topological differences are expected to affect rheological properties, as well as their direct interaction with structured biological substrates. Using a refined Martini-style coarse-grained model we describe the polymer-dependent differences in aggregation behaviour as well as selective interactions with a biomimetic model hair surface. Additionally, we introduce a formalism to characterize the response of the solution to shear as an initial study on lubrication properties, which define the sensorial performance of these systems in cosmetics (i.e., manageability, touch, etc.). The tools and techniques presented in this work illustrate the strength of molecular simulation in eco-design of formulation as a complement to experiment. These efforts help advance our understanding of how we can relate complex atomic-scale solution behaviour to relevant macroscopic properties. We expect these techniques to play an increasingly important role in advancing strategies for green polymer formulation design by providing an understanding for how new polymers could reach and even exceed the level of performance of existing polymers.

NRF2 in dermo-cosmetic: From scientific knowledge to skin care products.

The skin is the organ that is most susceptible to the impact of the exposome. Located at the interface with the external environment, it protects internal organs through the barrier function of the epidermis. It must adapt to the consequences of the harmful effects of solar radiation, the various chemical constituents of atmospheric pollution, and wounds associated with mechanical damage: oxidation, cytotoxicity, inflammation, and so forth. In this biological context, a capacity to adapt to the various stresses caused by the exposome is essential; otherwise, more or less serious conditions may develop accelerated aging, pigmentation disorders, atopy, psoriasis, and skin cancers. Nrf2-controlled pathways play a key role at this level. Nrf2 is a transcription factor that controls genes involved in oxidative stress protection and detoxification of chemicals. Its involvement in UV protection, reduction of inflammation in processes associated with healing, epidermal differentiation for barrier function, and hair regrowth, has been demonstrated. The modulation of Nrf2 in the skin may therefore constitute a skin protection or care strategy for certain dermatological stresses and disorders initiated or aggravated by the exposome. Nrf2 inducers can act through different modes of action. Keap1-dependent mechanisms include modification of the cysteine residues of Keap1 by (pro)electrophiles or prooxidants, and disruption of the Keap1-Nrf2 complex. Indirect mechanisms are suggested for numerous phytochemicals, acting on upstream pathways, or via hormesis. While developing novel and safe Nrf2 modulators for skin care may be challenging, new avenues can arise from natural compounds-based molecular modeling and emerging concepts such as epigenetic regulation.

Ethylated analogue of Zingerone: A new and eco-respectful preservative in cosmetics.

OBJECTIVE: This article describes the eco-design of a new preservative in cosmetics based on bio-inspiration of natural extracts from traditional medicines. In order to reach the multiple specification targets, various structures have been synthesized and evaluated to select the one demonstrating broad antimicrobial spectrum with favorable environmental profile and application potential to a wide variety of formulas. METHODS: In order to evaluate the antimicrobial activity of the synthesized structures, the method of the challenge test consisting in an artificial contamination of the sample with collection microbial strains and evaluation of the number of revivable microorganisms was used to select the most promising candidate. Validation of its antimicrobial potential was later confirmed on Gram positive and Gram negative bacteria, yeast and mold with measurement of its Minimum Inhibitory Concentration (MIC) in comparison with known preservatives. Environmental impact assessment of the selected candidate was achieved with the help of ready biodegradability and aquatic ecotoxicity tests performed according to appropriate Organization tes a strfor Economic Co-operation and Development (OECD) and European Union (EU) guidelinesy. RESULTS: Bio-inspired from turmeric and ginger extracts, an ethylated analog of Zingerone (EZ) with the chemical name 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one demonstrates the strongest activity on Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. Moreover, EZ shows a solubility in water two times higher than that of Zingerone thus increasing its interest as a potential preservative. Finally, its assessment of ready biodegradability and aquatic ecotoxicity in OECD-EU tests with a favorable environmental profile confirms its unique interest and fully justifies its use in cosmetic formulas as an eco-respectful preservative. CONCLUSION: Bio-inspiration based on technologies without noteworthy side effects but also on eco-design, particularly through the use of measures of potential environmental impact very upstream of a development, are two fundamental elements for the launching of new eco-friendly cosmetic ingredients. This approach has thus validated the strong potential of EZ as a preservative of eco-respectful formulas. The selection of EZ is also a very good example of the achievement of two key objectives targeted by cosmetic companies for the development of a novel active ingredient: environmental performance and technical performance.

OBJECTIF: Cet article décrit l'éco-conception d'un nouveau conservateur en cosmétique à partir de la bio-inspiration d'extraits naturels utilisées dans les médecines traditionnelles. Afin d'atteindre les cibles de spécification multiples, diverses structures ont été synthétisées et évaluées pour choisir celle qui présente un large spectre antimicrobien avec un profil environnemental favourable et un potentiel d'application pour une grande variété de formules. MÉTHODES: Afin d'évaluer l'activité antimicrobienne des structures synthétisées, la méthode du challenge test consistant en une contamination artificielle de l'échantillon par des souches microbiennes de collection suivie de l'évaluation du nombre de microorganismes revivifiables a été utilisée pour sélectionner le candidat le plus prometteur. La validation de son potentiel antimicrobien a par la suite été confirmée sur des bactéries à Gram positif et à Gram négatif, des levures et des moisissures grâce à la mesure de sa Concentration Minimale Inhibitrice (CMI) par rapport aux agents de conservation connus. L'évaluation de l'impact sur l'environnement du candidat sélectionné a été réalisée à l'aide de tests de biodégradabilité facile et d'écotoxicité aquatique réalisés selon les lignes directrices appropriées de l'Organization de Coopération et de Développement Economiques (OCDE). RESULTATS: Bio-inspiré des extraits de curcuma et de gingembre, un analogue éthylé de Zingerone nommé ETHYLZINGERONE (EZ) avec pour nom chimique 4-(3-ethoxy-4-hydroxyphenyl)butan-2-one démontre l'activité la plus forte sur Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa et Candida albicans. De plus, EZ montre une solubilité dans l'eau 2 fois supérieure à celle de la Zingerone renforçant ainsi son intérêt en tant que conservateur potentiel. Enfin, son évaluation dans les tests OCDE de la biodégradabilité facile et de l'écotoxicité aquatique avec un profil environnemental favourable confirme son intérêt unique et justifie pleinement son utilization dans les formules cosmétiques comme conservateur respectueux de l'environnement. CONCLUSION: La bio-inspiration basée sur des technologies sans effet secondaire notoire mais aussi l'éco-conception par l'utilization de mesures de l'impact environnemental potentiel très en amont d'un développement sont deux éléments fondamentaux pour la mise sur le marché de nouveaux ingrédients cosmétiques éco-respectueux. Cette approche a ainsi permis de valider le fort potentiel de EZ comme agent de conservation de formules respectueuses de l'environnement. La sélection de EZ est également un très bon exemple de l'atteinte de deux objectifs-clés recherchés par les entreprises cosmétiques pour le développement d'un nouvel actif: la performance environnementale et la performance technique.

Multi-dimensional computational pipeline for large-scale deep screening of compound effect assessment: an in silico case study on ageing-related compounds.

Designing alternative approaches to efficiently screen chemicals on the efficacy landscape is a challenging yet indispensable task in the current compound profiling methods. Particularly, increasing regulatory restrictions underscore the need to develop advanced computational pipelines for efficacy assessment of chemical compounds as alternative means to reduce and/or replace in vivo experiments. Here, we present an innovative computational pipeline for large-scale assessment of chemical compounds by analysing and clustering chemical compounds on the basis of multiple dimensions-structural similarity, binding profiles and their network effects across pathways and molecular interaction maps-to generate testable hypotheses on the pharmacological landscapes as well as identify potential mechanisms of efficacy on phenomenological processes. Further, we elucidate the application of the pipeline on a screen of anti-ageing-related compounds to cluster the candidates based on their structure, docking profile and network effects on fundamental metabolic/molecular pathways associated with the cell vitality, highlighting emergent insights on compounds activities based on the multi-dimensional deep screen pipeline.

Expression of NAD+ dependent 15-hydroxyprostaglandin dehydrogenase and protection of prostaglandins in human hair follicle.

NAD(+) dependent 15-hydroxyprostaglandin dehydrogenate (15-PGDH) catalyses oxidation of 15(S)-hydroxyl group of prostaglandins and as a result inactivates their physiological potential. Positive effects of prostaglandins or prostaglandin analogues were reported on terminal hair, vellus hair or eyelash growth and a complex prostaglandin network was recently described in human hair follicle. In the present study, we showed that 15-PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes, which brought us to consider this enzyme as a possible target to sustain local prostaglandin production. Using a recombinant enzymatic strategy, specific 15-PGDH inhibitors were screened. We identified a thiazolidine dione derivative exhibiting efficacy on follicular outer root sheath keratinocytes, since it concomitantly decreased the production of deactivated 13,14 dihydro 15-ketoprostaglandin F(2alpha) and sustained prostaglandin F(2alpha)in vitro production. In the context of recent interest in prostaglandins and prostaglandin analogues as hair regrowth agents, we postulated that the use of selected 15-PGDH inhibitors could reinforce or prolong the effect of these physiological mediators on hair and skin.